Talk:Β-Hydroxy β-methylbutyric acid
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The contents of the Calcium beta-hydroxy-beta-methylbutyrate page were merged into Β-Hydroxy β-methylbutyric acid. For the contribution history and old versions of the redirected page, please see its history; for the discussion at that location, see its talk page. |
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Reviews and CC-BY-2.0/CC-BY-4.0 diagrams
editDiagrams and reviews
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Most of these articles are currently available here. The file names reflect the ref names defined in the source code below. Seppi333 (Insert 2¢) 19:05, 23 May 2016 (UTC)
References
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Seppi333 (Insert 2¢) 20:36, 29 April 2016 (UTC)
- Thanks for posting those sources! I cannot believe how crappy that 2013 review is. Disturbing. Am going to open a discussion at WT:MED about it. Jytdog (talk) 18:16, 30 April 2016 (UTC)
- @Jytdog: I've only read (mostly) through half of these, but it appears that the reviews that describe HMB's effects in general (i.e., not solely in the context of a pharmacotherapy for sarcopenia/muscle wasting) - [1][2] - draw the same or even stronger conclusions about its effects in humans compared to the ISSN review. I'll probably end up relying on the newer reviews for supporting statements about clinical effects, so using this source to independently support such statements won't be an issue.
- Also, I'm considering taking this article to FA status since its primary clinical/therapeutic effect is unique and improving the article won't be too much work compared to other drug articles that I've worked on; there's only a handful of reviews and a few database refs from which to collate information on the compound, so finding all the relevant information to satisfy the comprehensiveness criterion won't be difficult (researching/revising amphetamine for FA took over a year; this would probably take ~1 month). With that in mind, if you have any feedback on the other sources or any other suggestions, I'd be interested to hear it. Seppi333 (Insert 2¢) 16:51, 20 May 2016 (UTC)
@Jytdog: Hey, sorry to bother you again with this request, but would you be willing to send me these 5 reviews?[3][4][5][6][7] They're paywalled and I don't have access. I'd really appreciate it. Seppi333 (Insert 2¢) 22:28, 23 May 2016 (UTC)
- I sent them all except PMID 23919746 which my library doesn't get. Jytdog (talk) 00:30, 24 May 2016 (UTC)
- Thank you very much! I appreciate it. Hopefully I can get that last one from WP:RX. Seppi333 (Insert 2¢) 05:08, 24 May 2016 (UTC)
December 2016
edit- Review of HMB's effects on skeletal muscle, pharmacodynamics, and pharmacokinetics from January 2016[8]
- Systematic review on supplements for cachexia from 2016[9]
Seppi333 (Insert 2¢) 19:15, 5 December 2016 (UTC)
References
- ^ Cite error: The named reference
Molecular Aspects of Medicine 2016 review
was invoked but never defined (see the help page). - ^ Cite error: The named reference
PEDs in sports 2015 review
was invoked but never defined (see the help page). - ^ Cite error: The named reference
HMB for cancer cachexia 2013 review
was invoked but never defined (see the help page). - ^ Cite error: The named reference
Effects of amino acid derivatives 2015 review
was invoked but never defined (see the help page). - ^ Cite error: The named reference
Nutrition supplements for athletes 2014 review
was invoked but never defined (see the help page). - ^ Duan Y, Li F, Li Y, Tang Y, Kong X, Feng Z, Anthony TG, Watford M, Hou Y, Wu G, Yin Y (January 2016). "The role of leucine and its metabolites in protein and energy metabolism". Amino Acids. 48 (1): 41–51. doi:10.1007/s00726-015-2067-1. PMID 26255285. S2CID 254080284.
- ^ Mochamat, Cuhls H, Marinova M, Kaasa S, Stieber C, Conrad R, Radbruch L, Mücke M (July 2016). "A systematic review on the role of vitamins, minerals, proteins, and other supplements for the treatment of cachexia in cancer: a European Palliative Care Research Centre cachexia project". Journal of Cachexia, Sarcopenia and Muscle. 8 (1): 25–39. doi:10.1002/jcsm.12127. PMC 5326814. PMID 27897391.
Recent preclinical research
edit- Covers HMB's effects on protein synthesis in brain cells, neurite outgrowth, and age-related dendritic remodeling in the brain of various nonhuman animals:
- Evidence that HMB is a (non-protein small molecule) neurotrophic factor in the brain of nonhuman animals (mice - in vitro/rats - in vivo)[1][2]
- Increases protein synthesis in the mouse brain (in vitro) and pig brain (in vivo)[1][3]
Seppi333 (Insert 2¢) 03:19, 28 May 2016 (UTC)
References
- ^ a b Salto R, Vílchez JD, Girón MD, Cabrera E, Campos N, Manzano M, Rueda R, López-Pedrosa JM (August 2015). "β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells". PLOS ONE. 10 (8): e0135614. Bibcode:2015PLoSO..1035614S. doi:10.1371/journal.pone.0135614. PMC 4534402. PMID 26267903.
In conclusion, we have shown for the first time that HMB promoted neurite outgrowth through PI3K/Akt and ERK1/2 signaling pathways in Neuro2a cells. Its effect in neuron differentiation is concomitant with higher levels of glucose transporters, the activation of mTOR by mTORC2 and consequently an increase in protein synthesis. Moreover, HMB is involved in promoting MEF2 activity and expression of members of this family of transcriptional factors. We believe that HMB may have great potential as [a neurotrophic] factor promoting neuron differentiation and plasticity. Our results indicated a novel effect of HMB on neurite outgrowth and call to further studies to reveal its positive influences on cognitive outcomes.
- ^ Kao M, Columbus DA, Suryawan A, Steinhoff-Wagner J, Hernandez-Garcia A, Nguyen HV, Fiorotto ML, Davis TA (May 2016). "Enteral β-Hydroxy-β-Methylbutyrate Supplementation Increases Protein Synthesis in Skeletal Muscle of Neonatal Pigs". Am. J. Physiol. Endocrinol. Metab. 310 (11): E1072–84. doi:10.1152/ajpendo.00520.2015. PMC 4935142. PMID 27143558.
The fractional rates of protein synthesis in the brain were greater in the piglets supplemented with HMB 40 and 80 or fed the HP diet compared to feeding the LP diet alone or the fasting condition (P < 0.05, Fig. 5, G).
mTOR signaling cascades
editLeaving this here for personal reference.
- Has a detailed mTOR signaling cascade diagram[1]
- Discusses and includes a diagram of signaling cascades involved in MPS/MPB[2] hosted here temporarily
Seppi333 (Insert 2¢) 08:51, 1 June 2016 (UTC) Updated 00:42, 27 August 2016 (UTC)
References
- ^ Lipton JO, Sahin M (October 2014). "The neurology of mTOR". Neuron. 84 (2): 275–291. doi:10.1016/j.neuron.2014.09.034. PMC 4223653. PMID 25374355.
Figure 2: The mTOR Signaling Pathway - ^ Anthony TG (July 2016). "Mechanisms of protein balance in skeletal muscle". Domest. Anim. Endocrinol. 56 Suppl (Suppl): S23–S32. doi:10.1016/j.domaniend.2016.02.012. PMC 4926040. PMID 27345321.
Metabolic pathway links
edit- HMB-CoA HMDB entry
- HMB-CoA KEGG entry
- alpha-Ketoisocaproate + O2 ⇒ 3-Hydroxy-3-methylbutyrate + CO2 – EC 1.13.11.27; 4-hydroxyphenylpyruvate dioxygenase = KIC dioxygenase per [1][2]
Should be able to write a comprehensive biosynthesis/metabolism section using these 5 refs:
- [1] (covers α-KIC → HMB reaction)
- [2] (covers most of the metabolic pathway; has another diagram)
- [3] (covers HMB-CoA → HMB)
- [4] (covers most of the metabolic pathway; includes the same metabolic pathway graphic as the ISSN review)
- ISSN review - PMID 23374455 (review with the article's current metabolic pathway graphic)
Seppi333 (Insert 2¢) 00:10, 7 June 2016 (UTC)
References
- ^ a b "Homo sapiens: 4-hydroxyphenylpyruvate dioxygenase reaction". MetaCyc. SRI International. 20 August 2012. Retrieved 6 June 2016.
- ^ a b Kohlmeier M (2015). "Leucine". Nutrient Metabolism: Structures, Functions, and Genes (2nd ed.). Academic Press. pp. 385–388. ISBN 9780123877840.
Figure 8.57: Metabolism of L-leucine
{{cite book}}
: External link in
(help)|quote=
- ^ Mock DM, Stratton SL, Horvath TD, Bogusiewicz A, Matthews NI, Henrich CL, Dawson AM, Spencer HJ, Owen SN, Boysen G, Moran JH (November 2011). "Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans". J. Nutr. 141 (11): 1925–1930. doi:10.3945/jn.111.146126. PMC 3192457. PMID 21918059.
Reduced activity of MCC impairs catalysis of an essential step in the mitochondrial catabolism of the BCAA leucine. Metabolic impairment diverts methylcrotonyl CoA to 3-hydroxyisovaleryl CoA in a reaction catalyzed by enoyl-CoA hydratase (22, 23). 3-Hydroxyisovaleryl CoA accumulation can inhibit cellular respiration either directly or via effects on the ratios of acyl CoA:free CoA if further metabolism and detoxification of 3-hydroxyisovaleryl CoA does not occur (22). The transfer to carnitine by 4 carnitine acyl-CoA transferases distributed in subcellular compartments likely serves as an important reservoir for acyl moieties (39–41). 3-Hydroxyisovaleryl CoA is likely detoxified by carnitine acetyltransferase producing 3HIA-carnitine, which is transported across the inner mitochondrial membrane (and hence effectively out of the mitochondria) via carnitine-acylcarnitine translocase (39). 3HIA-carnitine is thought to be either directly deacylated by a hydrolase to 3HIA or to undergo a second CoA exchange to again form 3-hydroxyisovaleryl CoA followed by release of 3HIA and free CoA by a thioesterase.
FAC-related references
editFor Nergaal's review
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References
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For Jytdog's review
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For Nergaal+Axl's reviews (History section content)
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References
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Upcoming systematic review
edit"Beta-hydroxy-beta-methylbutyrate free acid improves resistance training-induced muscle mass and function: a systematic review" - anticipated completion (publication?) date: September 2016
- Research question: What is the effect of HMB-FA on resistance training-induced muscle mass and function?
- Primary outcomes:
- Effects on skeletal muscle in sedentary, active and recreationally-trained subjects and HMB-supplemented compared with placebo.
- Change in lean mass from baseline to final intervention.
- Change in strength and biochemical parameters from baseline to final intervention.
Comment about safety
editI'd like to start off by stating that I hope my commenting here does not turn away any potential GA reviewers since I believe these concerns can be addressed quickly, so much so that I'm tempted to go ahead and make them myself rather than post here, but I believe the prose will be more consistent if these changes are made by those who have written the majority of the article already.
In the opening there is a stand-alone sentence discussing HMB's safety in "young or old individuals", but to me that is a little unclear. The first source cited for that statement says "Chronic consumption of HMB is safe in both young and old populations", so I looked through it to see what they consider young. It appears they are referring to young adults as later in the paper they state that no research has been carried out on infants and very little research has been carried out on adolescents. Additionally no research appears to have been carried out on pregnant women.
With this in mind I would suggest further clarifying in the lead the lower bound of the age of individuals for which HMB supplementation appears safe. In addition the description of its safety in humans in the side effects section should be qualified so that it excludes human sub-populations that HMB hasn't been well studied in. Lastly the first sentence of that section implies that safety for animals in general has been established—"the safety profile of HMB in humans and animals"—this should be reworded/expanded to convey either which animals it has been found to be safe for, and/or to describe how animal models have been used to help establish the safety profile in humans. M. A. Bruhn (talk) 05:13, 3 August 2016 (UTC)
- @M. A. Bruhn: I agree that this should be clarified.
- I think specifying "young adults and older adults" should adequately address the ambiguity in the current phrasing. I actually wasn't aware that any clinical testing with the compound had been conducted on individuals who are younger than 18.
- I imagine that based upon the current wording, one might infer that its safety status has been shown to be analogous to a US pregnancy category A drug; this isn't true, since as far as I know there hasn't been any RCT testing with HMB supplementation on pregnant women. While it's very likely true that the compound isn't teratogenic, we can't say this and it shouldn't be implied without an appropriate citation. I'll add a clause stating that no clinical testing has been conducted with supplemental HMB in pregnant women.
- I'd intended to add data on toxicity testing in animal models earlier but later decided to forego it since I figured most people would be interested in clinical information in humans. If you think it's worth adding, I'd be happy to include this.
IIRC, animal testing has involved daily doses of 15 g in rats for a duration of 1+ months w/o adverse effects, but I'll need to double check that.(edit: the doses given to rats were actually much higher based upon PMID 23374455 and PMID 25099672) I'll add the information about the animal, dose/dosage, and duration of testing to the article sometime today or tomorrow when I find the review that covers it. As for humans, clinical testing has involved 3 g daily doses for up to a year w/o adverse effects and 6 g daily doses for a couple of months w/o adverse effects in young adults. This would probably also be worth mentioning in the side effects section, so I'll include this as well when I add the information on animal testing.
On a related note, the only thing I could probably put into an OD section is the LD50 for rodent species; since LD50 in non-human animals seldom accurately reflects the LD50 for humans, I decided to forego the overdose section altogether.
- I'll start working on making these changes now. Please let me know if you have any other suggestions for improvement; I'd be happy to act on them. Also, feel free to edit the article yourself and make any changes that you know are supported by references. I don't bite. Seppi333 (Insert 2¢) 06:02, 3 August 2016 (UTC)
- I'm going to add the information on high-dose animal testing a little later since I need to log off for now. I think I've addressed most of the issues you've raised here, so let me know what you think when you get a chance. Seppi333 (Insert 2¢) 07:23, 3 August 2016 (UTC)
- Those changes have mostly addressed everything for me. The only concern I have is with the ambiguity of "animals". From the context it can be reasonably inferred by the average reader to refer to animals commonly used in research to predict effects in humans, but not all readers might make inference. Although it's unlikely that someone's going to believe it's referring to coral reefs and bumble bees, the statement as it is presently worded is grammatically stating that HMB is safe for animals in general. I think it just needs to be slightly reworded so that instead stating "The safety profile of HMB in ... animals has been well-established...” it instead more explicitly conveys that the animals which HMB appears safe in are animals used to gauge safety for humans. Maybe something along the lines of "The safety profile of HMB in adult humans has been well-established by medical reviews looking at a combination of randomized controlled trials in humans as well as extensive animal testing." I haven't read the medical reviews so I don't know if this is a good characterization or not.
- I agree that data on animal models is probably irrelevant to add. I said that information on safety of specific animals could be added just on the off chance that there was information that was useful in it of itself, for instance if there had been any research on using HMB supplementation to bulk up livestock. But if that's not the case then there wouldn't seem to be a reason to make any specific mention of animal testing except in cases where it introduces something that human testing hasn't covered, such as with the pregnant pigs. I think making an OD section just for the LD50 might be giving it undue weight. I notice that the chem infoboxes have an LD50 parameter but the drug infoboxes do not, so perhaps that is an indication that LD50's for drugs shouldn't be presented in the infoboxes either. I'm neither for or against addition of such information, and think you should just do what you prefer.
- I'll let you know if I see anything else or feel free to do it myself. Thanks and good luck with your editing.M. A. Bruhn (talk) 08:35, 3 August 2016 (UTC)
- I used your proposed wording, which was accurate, and indicated that most of the animal testing has involved lab rats, pigs, chickens, and turkeys. Edit: the review on HMB supplementation in animals (PMID 25099672) states that "
the utility of HMB supplementation in animals has been shown in numerous studies, which have demonstrated enhanced body weight gain and carcass yield in slaughter animals
", but I'm going to look for other sources that cover its use in livestock for this purpose before covering it in the article since I don't know how common/notable this practice is. Seppi333 (Insert 2¢) 09:24, 3 August 2016 (UTC); edited at 14:17, 3 August 2016 (UTC)
- I used your proposed wording, which was accurate, and indicated that most of the animal testing has involved lab rats, pigs, chickens, and turkeys. Edit: the review on HMB supplementation in animals (PMID 25099672) states that "
- I'm going to add the information on high-dose animal testing a little later since I need to log off for now. I think I've addressed most of the issues you've raised here, so let me know what you think when you get a chance. Seppi333 (Insert 2¢) 07:23, 3 August 2016 (UTC)
@M. A. Bruhn: How would you feel about the addition of this statement to the paragraph on pregnancy?
As of 2016[update], Metabolic Technologies Inc., the company that grants licenses to include HMB in dietary supplements, advises pregnant and lactating women not to take HMB due to a lack of safety studies conducted with this population.[1]
I'm hesitant to add this, although I think it's notable since this is the company that grants licenses to allow the inclusion of HMB in dietary supplements. The reference is a primary source for the statement, but the statement itself is advisement as opposed to a medical claim. Seppi333 (Insert 2¢) 02:45, 23 August 2016 (UTC)
- Edit: I decided to add this material to a newly created "Contraindications" section, since IMO this content is most appropriate there. Seppi333 (Insert 2¢) 04:19, 23 August 2016 (UTC)
- I'm not sure how I feel about this source's inclusion. Companies will produce statements instructing consumers not to use their products in certain ways simply because 1) they want to avoid liability and 2) they know their consumers will ignore them anyways (like with consumers using Q-tips to clean their ears). When you first posted I spent some time trying to find a more MEDRS compliant source to use instead, I found several RS sources, but no MEDRS though. If it is qualified as "Company X says Y" then it isn't really an issue of accuracy (since they do indeed state this) so much as weight. I'm not sure if it is undue weight or not. If this were a drug then it would be easy to find alternative sources, but since it is a supplement our options are limited. I suppose I am leaning more towards its inclusion, but would prefer it if a better source could replace it. M. A. Bruhn (talk) 06:42, 29 August 2016 (UTC)
- fwiw I think that Seppi is trying like crazy to cover all the sections in MEDMOS and cover the things we usually cover; for medicines we usually give the formal pregnancy category. A drug label will generally give the information as to whether the drug has been tested in pregnant women, or not and the label will give the negative information. In this case neither the label for Juven nor the label for the medical food Ensure discusses pregnancy. Neither of the current FDA draft guidances on medical food (not this and not this discuss pregnancy categories, and I am ~guessing~ that this is because medical food is well, food. Not something strange like a drug.
- Because of all that, Seppi, I think there is no need to talk about the pregnancy thing; not until this is marketed as a drug (which I am guessing it never will be)
- That said, I still think including the statement by the company, with attribution as suggested by M A Bruhn above, is a very good move. Jytdog (talk) 07:00, 29 August 2016 (UTC)
- Yeah... I've been looking for medical sources that make a statement about HMB use during pregnancy or that cover a rather obvious drug interaction between HMB and rapamycin and/or mTOR inhibitors in general, but haven't really found suitable sources for either. In the case of the pregnancy statement in the article, I figure I can get away with that source since it doesn't really make any medical claims about HMB. It's basically just the company's advice, so I agree that it is more of a WP:DUE issue than a WP:RS/MEDRS issue.
- As for the HMB/rapamycin interaction, their opposing effects on MTORC1 activation and protein synthesis is mentioned only in this primary source, which I can't use to cite a drug interaction. Seppi333 (Insert 2¢) 21:09, 29 August 2016 (UTC)
- I'm not sure how I feel about this source's inclusion. Companies will produce statements instructing consumers not to use their products in certain ways simply because 1) they want to avoid liability and 2) they know their consumers will ignore them anyways (like with consumers using Q-tips to clean their ears). When you first posted I spent some time trying to find a more MEDRS compliant source to use instead, I found several RS sources, but no MEDRS though. If it is qualified as "Company X says Y" then it isn't really an issue of accuracy (since they do indeed state this) so much as weight. I'm not sure if it is undue weight or not. If this were a drug then it would be easy to find alternative sources, but since it is a supplement our options are limited. I suppose I am leaning more towards its inclusion, but would prefer it if a better source could replace it. M. A. Bruhn (talk) 06:42, 29 August 2016 (UTC)
Reflist
editReferences
- ^ "Who should not take HMB?". Metabolic Technologies, Inc. Retrieved 23 August 2016.
Pregnant or lactating women are advised against taking HMB because safety studies have not yet been conducted for these populations.
Page name
editThe page name doesn't seem to be the most obvious choice to be. Thinking about WP:NAMINGCRITERIA I might suggest as alternatives (in rough order of preference):
- HMB, on the grounds of Conciseness and Recognizability. It might then require the existing HMB to be moved to HMB (disambiguation)
- beta-hydroxyisovaleric acid, on the grounds of Naturalness (MESH heading term)
- 3-hydroxy-3-methylbutanoic acid, on the grounds of Precision (IUPAC name)
Thoughts? If there is a decision for no change, then I think the last 2 terms should also be redirects here. Klbrain (talk) 18:38, 3 August 2016 (UTC)
- I'll respond to these in reverse order:
- 3-hydroxy-3-methylbutanoic acid is neither more nor less precise than the current article name, both names only specify one molecule.
- The main issue with beta-hydroxyisovaleric acid is that the common acronym, HMB, doesn't work for it. Additionally it seems that it isn't the preferred term in current literature.
- There are specific naming guidelines based off of the topic. WP:NCMED gives the naming guidelines for medical articles and states "The article title should be the scientific or recognised medical name that is most commonly used in recent, high-quality, English-language medical sources". Furthermore it states that drugs should be titled based off their International Nonproprietary Name, although I'm fairly certain HMB does not have an INN, and the line between drug and supplement is blurry. The chemistry naming guidelines at WP:NCCHEM generally recommend this quoted section from the general naming conventions: "Generally, article naming should give priority to what the majority of English speakers would most easily recognize, with a reasonable minimum of ambiguity, while at the same time making linking to those articles easy and second nature". I think it might be best to look at other dietary supplements for guidance, and looking at other dietary supplement articles it appears using an acronym in place of the chemical name is not normally done, although perhaps a broader discussion should be had on the topic in a more general forum. M. A. Bruhn (talk) 20:46, 3 August 2016 (UTC)
- The vast majority of literature that has been published on this compound from the past 20 years has used the terms "β-hydroxy β-methylbutyrate" [213 hits] or "β-hydroxy β-methylbutyric acid" [10 hits] (some sources also hyphenate "hydroxy-β"), depending on whether the study involved the conjugate base or acid. Prior to that, the 3- and β- "hydroxyisovalerate/hydroxyisovaleric acid" terms were more common. For comparison, the MESH name "beta-hydroxyisovaleric acid" gets only 8 results out of the 247 papers that are found from an unfiltered search using any of the MESH-indexed synonyms. The IUPAC name is seldom used in published literature.
- Most commercial products contain the calcium salt of this compound and refer to it as "calcium hydroxymethylbutyrate", "calcium β-hydroxy β-methylbutyrate", or "calcium β-hydroxy β-methylbutyrate monohydrate" (again, some also hyphenate "hydroxy-β"), so I imagine that most of the incoming traffic to this article uses one of those terms. I'm more inclined to use the conjugate base as the page name since it's more prevalent in published literature, but it seems more common to use the acid than the base as the page title when there aren't separate articles for the conjugate acid/base forms of a compound (in this case, the acid/base forms of HMB should be covered in the same article). Consequently, I think the current page name is acceptable even though it's not the most common name. I'm open to renaming the article though. Seppi333 (Insert 2¢) 22:01, 3 August 2016 (UTC)
New sources
edit@Jytdog: Thanks for doing a literature search and posting these sources here; I really appreciate it! I'll read through and use them to write new content when I get a chance later today or tomorrow. Seppi333 (Insert 2¢) 21:26, 9 September 2016 (UTC)
- I've been busier than I expected off-wiki over the past few days. I should have time to follow-up on this tomorrow night. Seppi333 (Insert 2¢) 22:48, 12 September 2016 (UTC)
- @Jytdog: My bad for not doing this yet; I'm going to stop trying to give myself further deadlines that I can't meet due to how busy I've been this past week. I will, however, use the sources that you linked below to add content before I look for sources to cite for adding a statement on the calcium content of HMB-Ca. Seppi333 (Insert 2¢) 23:40, 16 September 2016 (UTC)
- That's OK - the fitzpatrick book is already used and there is not much else here that is useful. I was mostly recording my work actually trying to track down sales.. Jytdog (talk) 23:43, 16 September 2016 (UTC)
- @Jytdog: Oh. Well, I'll still look through them anyway - might have something worth adding. Also, one of the refs that you linked to at FAC mentioned something you might be interested in (see the bold+underlined text below). As of when this ref was published, all of MTI's products contained HMB, as stated in the quote. As of now, they also sell or license one product which contains no HMB: an adenosine triphosphate (ATP) supplement which they call "betaATP". Seppi333 (Insert 2¢) 00:44, 17 September 2016 (UTC)
- FWIW, based upon the prices of currently available HMB-Ca and HMB-FA supplements and the relative efficacy in primary studies between HMB-FA and HMB-Ca, I really doubt MTI is making close to $10,000,000 annually on HMB-FA alone. Seppi333 (Insert 2¢) 00:51, 17 September 2016 (UTC)
- @Jytdog: Oh. Well, I'll still look through them anyway - might have something worth adding. Also, one of the refs that you linked to at FAC mentioned something you might be interested in (see the bold+underlined text below). As of when this ref was published, all of MTI's products contained HMB, as stated in the quote. As of now, they also sell or license one product which contains no HMB: an adenosine triphosphate (ATP) supplement which they call "betaATP". Seppi333 (Insert 2¢) 00:44, 17 September 2016 (UTC)
- That's OK - the fitzpatrick book is already used and there is not much else here that is useful. I was mostly recording my work actually trying to track down sales.. Jytdog (talk) 23:43, 16 September 2016 (UTC)
- @Jytdog: My bad for not doing this yet; I'm going to stop trying to give myself further deadlines that I can't meet due to how busy I've been this past week. I will, however, use the sources that you linked below to add content before I look for sources to cite for adding a statement on the calcium content of HMB-Ca. Seppi333 (Insert 2¢) 23:40, 16 September 2016 (UTC)
Metabolic Technologies 2011 sales + 5-year sales projections
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sources for extent of use of HMB
editam looking for sources for this, will record what I find here. others are free to add of course...
This is really hard as MTI is a private company so have no obligation (and don't) report sales.
- Shelly Meltzer, Cecily Fuller (2007). The Complete Book of Sports Nutrition: A Practical Guide to Eating for Sport. New Holland Publishers. p. 94. ISBN 9781845370817. -- says that 10,300 athletes at the 2000 Summer Olympics were tested for doping, and of them, 2758 were surveyed about their use of supplements. 24 of them said they used HMB. (for comparison, 1996 used some kind of vitamin)
- Nuckols, Greg (July 20, 2016). "The HMB Controversy: Better than Steroids?". Strengtheory. (not a great ref, but guy who runs it seems to be not insignificant in world of lifers, see here). Has a blog entry focused on primary sources PMID 24599749 published in 2014 and the followup PMID 24714541 published this July and their remarkable results, and writes: "A supplement that’s been around for a long time, but which isn’t all that popular, works better than steroids?". "which isn't all that popular". Not much but something.
- Eichner, E. Randy; King, Douglas; Myhal, Mark; Prentice, Bill; Ziegenfuss, Tim N. (1999). "Roundtable: "Muscle Builder" Supplements" (PDF). RT#37. 10 (3). again really slim. From 1999. One of roundtable participants says: "HMB sales declined rapidly after it was introduced because it had no perceived effect on muscle mass and was expensive." Same person also said: "Likewise, HMB has not lived up to its marketing hype as an anabolic agent" Another, " Among athletes who want to gain muscle mass, protein and creatine supplements are popular, especially in football, wrestling, and track and field. HMB and the banned substances DHEA and the “andros” are used by few or none"
This is all I found in a google search 10 pages out. Will check my library... Jytdog (talk) 21:10, 9 September 2016 (UTC)
sources on business background and marketing
edit- Fitzgerald M (2014). Diet Cults: The Surprising Fallacy at the Core of Nutrition Fads and a Guide to Healthy Eating for the Rest of US. Pegasus Books. p. 147. ISBN 978-1-60598-595-4. -- has a passage describing the origin of Metabolic Technologies. Also discusses the science a bit - says early research was hyped, and notes the 2009 review that found it had some benefit for people just starting a training regimen but not for people who have been at it longterm.
- Conis, Elena (29 May 2011). "Muscle drink with HMB targets the middle-aged". Los Angeles Times. -- "hook" was launch of Ensure Muscle Health; discusses that HMB is marketed to older/middle aged folks who want to start getting into shape, because that is who benefits the most (citing the 2009 review again)
- Kane, Ed (September 2014). "Nutritional Supplements in Horses" (PDF). Insider. Animal Health International, Inc. pp. 11–15. - a trade rag, notes that HMB is marketed for horses but there is "little to no data to support its use in horses".
Same search as above. Jytdog (talk) 21:10, 9 September 2016 (UTC)
Mg of ionic calcium per gram of pure HMB from HMB-Ca
editNeed to find a WP:RS-quality source for this, since I think it's worth covering. Probably should be mentioned in the article since the {{mineral supplements}}
navbox links here and most HMB-Ca brands don't appear to list this information on the supplement bottles. Seppi333 (Insert 2¢) 23:40, 16 September 2016 (UTC)
Placement of biosynthesis section
editBiosynthesis is currently a subsection pharmacology/pharmacokinetics. Pharmacokinetics is what the body does to the drug, not how the body synthesizes it. Also some bugs and I assume many other "critters" synthesize HMB. Hence logically biosynthesis should not be a subsection of pharmacokinetics, but rather the chemistry (or possibly a new biochemistry) section. The reason I ask is that MC-CoA is used in the biosynthesis of a tetrasaccharide produced by Bacillus anthracis (anthrax bacteria) and HMB itself has been used in the laboratory synthesis of this tetrasaccharide (see PMID 15152001, 20614885). This new material would not be appropriate to add to the pharmacokinetics section but would be appropriate in a new biochemistry section. Thoughts? Boghog (talk) 09:13, 25 September 2016 (UTC)
- I'm okay with moving it. I recognized that it wasn't really relevant to the PK section when I created it under that heading, but I put it there anyway simply because the HMB metabolism diagram also illustrates HMB biosynthesis. Seppi333 (Insert 2¢) 10:33, 25 September 2016 (UTC)
Expansion of chemistry section
editWith thanks to Sizeofint for supplying database searches, I have expanded the synthesis section. There are several more syntheses that could be added, but most of these are obscure reactions or reactions where HMB is a side product. Hence I question the notability of these. Also there were some early syntheses reported (and associated physical data of the synthesized HMB) based on an aldol condensation without dehydration between acetone and ethyl acetate. However I think this would be highly unlikely since the dehydration is the driving force for the reaction. As far as physical data, there is not much more that could (or should) be added. By far, the most notable aspect of HMB is that is a naturally produced metabolite and a food additive . Much less has been published about its chemistry. Hence per WP:DUE, it is appropriate that the chemistry section of this article is significantly shorter than some of the other sections. Boghog (talk) 09:35, 25 September 2016 (UTC)
- @Boghog: you should probably post this in Nergaal's review section to discuss with him what should or could be added about to HMB's chemistry. He's the only reviewer who has commented on the chemistry section thus far. Seppi333 (Insert 2¢) 17:52, 26 September 2016 (UTC)
History → Synthesis section split
edit@Boghog: I split part of the material that you added to the history section to the synthesis section and re-added a slightly duplicate statement about its very first reported synthesis to the history section in this edit. Is that okay with you? Seppi333 (Insert 2¢) 16:52, 9 November 2016 (UTC)
- Yes. I was thinking of doing something similar. Thanks for taking care of that. Boghog (talk) 17:32, 9 November 2016 (UTC)
In the body
editFollow-up from FAC
editThe content in this tab has been moved again; it's now located at Wikipedia:Featured article candidates/Beta-Hydroxy beta-methylbutyric acid/archive3#Comments by Doc James.
Please continue this discussion there. | ||
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The review you are using comes to three sentences of conclusions "HMB contributed to preservation of muscle mass in older adults." which says it help keep mm mass, does not comment on those with sarcopenea. "HMB supplementation may be useful in the prevention of muscle atrophy induced by bed rest or other factors." A decrease of uncertainty "Further studies are needed to determine the precise effects of HMB on muscle strength and physical function in older adults." Means it is unclear if HMB affects str or function. Doc James (talk · contribs · email) 03:04, 17 December 2016 (UTC)
@Doc James: What is your concern with that sentence, specifically, if the population samples included in the RCTs from that meta-analysis (link here) wasn't the issue? Seppi333 (Insert 2¢) 00:00, 20 December 2016 (UTC)
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New reviews
editChecked for updates on November 9th, 2017 (my birthday, yay). Seppi333 (Insert 2¢) 05:33, 9 November 2017 (UTC)
- Happy Birthday :-) Doc James (talk · contribs · email) 05:37, 9 November 2017 (UTC)
- Thanks! Seppi333 (Insert 2¢) 06:12, 9 November 2017 (UTC)
- Happy Birthday :-) Doc James (talk · contribs · email) 05:37, 9 November 2017 (UTC)
1st
editAdded (partially) - more potential material to go through and add if deemed encyclopedic; see collapse tab below
- @Jytdog, Boghog, and Doc James: I just did a literature search and found one new review: PMID 28493406;[1] it was published online on May 10, 2017. Also, I contacted the corresponding author of this prospective systematic review a few weeks ago; he told me that it has been submitted to an academic journal and is currently being peer-reviewed, so I suspect that it will be published within the next 1–3 months. Once it's published, I intend to add a summary of its findings on the effects/efficacy of HMB in healthy individuals.
As for this[1] review, I intend to use it to cite existing statements and possibly add new material which is relevant to clinical uses (e.g., HMB supplementation in elderly/sarcopenic individuals). These are the sections from the review that are relevant to its clinical uses:
Excerpts of the sections on Elderly populations, Toxicity + adverse effects, and Conclusions
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Also, check for new pharmacology content to add from these sections of the review:
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Most of the quoted material above is already covered to some extent in the article at the moment, but the commentary from this review isn't reflected in the current article text. Should new content be added, or should this reference just be appended to existing text that it supports? Do any of you have any proposed revisions to the article in mind? @Doc James: I'm directing that last question mainly at you since you took issue with how some of the medical statements were worded during the most recent FAC nomination. Seppi333 (Insert 2¢) 04:27, 3 June 2017 (UTC)
2nd
edit- "A systematic review on β-hydroxy-β-methylbutyrate free acid supplementation suggests improvements in measures of muscle recovery, performance, and hypertrophy following resistance training."[2]
@Boghog, Jytdog, and Doc James: The "#Upcoming systematic review" was finally published in an academic journal in September.[2] Boghog, do you think we should renominate the article for FA or continue with GAN once I add coverage of this review and the other reviews listed below to the article? Seppi333 (Insert 2¢) 04:48, 9 November 2017 (UTC)
- FYI: I'm waiting to get ref #5 below (PMID 28554316) from WP:RX before I update the article with the content from all of the reviews cited in this section (i.e., the ones in #Section reflist). Seppi333 (Insert 2¢) 01:13, 19 November 2017 (UTC)
3rd–8th
edit- Pharmacological targeting of exercise adaptations in skeletal muscle: Benefits and pitfalls – October 2017 review.[3]
- The Potential of β-Hydroxy-β-Methylbutyrate as a New Strategy for the Management of Sarcopenia and Sarcopenic Obesity – October 2017 review.[4] Added
- Beta-hydroxy-beta-methyl butyrate (HMB): From experimental data to clinical evidence in sarcopenia – May 2017 review[5]
- What factors influence protein synthesis and degradation in critical illness? – March 2017 review.[6]
-
Ergogenic Aids in Sports – February 2017 review (in Spanish - would probably only cite material covered in the abstract if this review is used).[7] - Efficacy and Safety of Leucine Supplementation in the Elderly – December 2016 review.[8]
Seppi333 (Insert 2¢) 05:19, 9 November 2017 (UTC) – Updated 06:12, 9 November 2017 (UTC)
- Yes this ref says "Clinical trials performed in older adults confirm that HMB can attenuate the progression of sarcopenia in elderly subjects." So basically it may slow muscle loss.[6]
- This review is a little more cautious concluding "However, heterogeneous methodological approaches preclude solid conclusions, and more studies are needed to confirm the role of HMB as a promising agent to treat sarcopenia."[7]
- So definitely promising and appears safe but not yet definite. Doc James (talk · contribs · email) 05:44, 9 November 2017 (UTC)
- @Doc James: I had to contact Dr. Alfonso Cruz-Jentoft via email to obtain his review article (i.e., the one that you mentioned was a little more cautious in your reply immediately above) since no one at WP:RX had access to the journal in which he published his review. You can read his review and its conclusions here. Seppi333 (Insert 2¢) 18:22, 17 December 2017 (UTC)
- HMB increases myofibrillar protein synthesis by upregulation via the mTOR pathway. - HMB modulates protein degradation by inhibiting the ubiquitin-proteasome proteolytic pathway in muscle cells. Ubiquitin is induced by immobilization and by catabolic conditions, inducing proteasome expression through the activation of nuclear factor kappa B (NK-κB), thus promoting muscle wasting. HMB may inhibit the activity of NK-κB, attenuating muscle loss in wasting conditions. - The integrity of cell membranes depends on cholesterol synthesis from acetyl-CoA. HMB is converted to ß-hydroxyß- methylglutaryl-coenzyme A (HMG-CoA), which is turned into cholesterol by the HMG-coenzyme A reductase, the rate-limiting enzyme to cholesterol synthesis. Thus, HMB supplementation may stabilize cell membranes. HMB itself seems to be a component of cell membranes. - HMB may prevent cell apoptosis and enhance muscle satellite cell survival. - HMB increases proliferation and differentiation of muscle stem cells, via the MAPK/ERK and PI3K/Akt pathways. - HMB up-regulates transcription and expression of the IGF-I gene in skeletal muscle and liver. IGF exerts an anabolic action and causes hypertrophy of skeletal muscle fibers. |
Pharmacodynamics and pharmacokinetics of HMB-CA in humans in vivo
edit- This is a primary source which examines the same pharmacodynamic and pharmacokinetic parameters for HMB-CA as the ones that were examined in the study on HMB-FA and leucine which is currently cited in the article – October 2017 primary study.[9] Seppi333 (Insert 2¢) 06:12, 9 November 2017 (UTC)
- Already cited in the article (this is the study on HMB-FA and leucine that was mentioned immediately above).[10]
Section reflist
editReferences
- ^ a b c d e Holeček M (May 2017). "Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions". Journal of Cachexia, Sarcopenia and Muscle. 8 (4): 529–541. doi:10.1002/jcsm.12208. PMC 5566641. PMID 28493406.
- ^ a b Silva VR, Belozo FL, Micheletti TO, Conrado M, Stout JR, Pimentel GD, Gonzalez AM (September 2017). "β-hydroxy-β-methylbutyrate free acid supplementation may improve recovery and muscle adaptations after resistance training: a systematic review". Nutrition Research. 45: 1–9. doi:10.1016/j.nutres.2017.07.008. hdl:11449/170023. PMID 29037326.
HMB's mechanisms of action are generally considered to relate to its effect on both muscle protein synthesis and muscle protein breakdown (Figure 1) [2, 3]. HMB appears to stimulate muscle protein synthesis through an up-regulation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), a signaling cascade involved in coordination of translation initiation of muscle protein synthesis [2, 4]. Additionally, HMB may have antagonistic effects on the ubiquitin–proteasome pathway, a system that degrades intracellular proteins [5, 6]. Evidence also suggests that HMB promotes myogenic proliferation, differentiation, and cell fusion [7]. ... Exogenous HMB-FA administration has shown to increase intramuscular anabolic signaling, stimulate muscle protein synthesis, and attenuate muscle protein breakdown in humans [2].
- ^ Weihrauch M, Handschin C (October 2017). "Pharmacological targeting of exercise adaptations in skeletal muscle: Benefits and pitfalls". Biochemical Pharmacology. 147: 211–220. doi:10.1016/j.bcp.2017.10.006. PMC 5850978. PMID 29061342.
- ^ Rossi AP, D'Introno A, Rubele S, Caliari C, Gattazzo S, Zoico E, Mazzali G, Fantin F, Zamboni M (October 2017). "The Potential of β-Hydroxy-β-Methylbutyrate as a New Strategy for the Management of Sarcopenia and Sarcopenic Obesity". Drugs & Aging. 34 (11): 833–840. doi:10.1007/s40266-017-0496-0. PMID 29086232. S2CID 4284897.
Clinical trials performed in older adults confirm that HMB can attenuate the progression of sarcopenia in elderly subjects. HMB supplementation results in an increase in skeletal muscle mass and strength in the elderly and its effect is even greater when combined with physical exercise.
- ^ Cruz-Jentoft AJ (May 2017). "Beta-hydroxy-beta-methyl butyrate (HMB): From experimental data to clinical evidence in sarcopenia". Current Protein & Peptide Science. 18 (7): 668–672. doi:10.2174/1389203718666170529105026. PMID 28554316.
HMB is widely used as an ergogenic supplement by young athletes.
- ^ Di Girolamo FG, Situlin R, Biolo G (March 2017). "What factors influence protein synthesis and degradation in critical illness?". Current Opinion in Clinical Nutrition and Metabolic Care. 20 (2): 124–130. doi:10.1097/MCO.0000000000000347. PMID 28002075. S2CID 3480306.
- ^ omitted - not planning to use this review
- ^ Borack MS, Volpi E (December 2016). "Efficacy and Safety of Leucine Supplementation in the Elderly". The Journal of Nutrition. 146 (12): 2625S–2629S. doi:10.3945/jn.116.230771. PMC 5118760. PMID 27934654.
No serious side effects have been reported with leucine, EAA, or HMB supplementation; and the health risks associated with these supplements are few and predictable.
- ^ Wilkinson DJ, Hossain T, Limb MC, Phillips BE, Lund J, Williams JP, Brook MS, Cegielski J, Philp A, Ashcroft S, Rathmacher JA, Szewczyk NJ, Smith K, Atherton PJ (October 2017). "Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism". Clinical Nutrition (Edinburgh, Scotland). 37 (6): 2068–2075. doi:10.1016/j.clnu.2017.09.024. PMC 6295980. PMID 29097038.
Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 μM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < [0.001]) and suppressions in MPB (PA: 7.6 ± 1.2 μmol Phe per leg min-1, Ca-HMB: 5.2 ± 0.8 μmol Phe per leg min-1, p < 0.01). ... During the first 2.5 h period we gathered postabsorptive/fasted measurements, the volunteers then consumed 3.42 g of Ca-HMB (equivalent to 2.74 g of FA-HMB) ... It may seem difficult for one to reconcile that acute provision of CaHMB, in the absence of exogenous nutrition (i.e. EAA's) and following an overnight fast, is still able to elicit a robust, perhaps near maximal stimulation of MPS, i.e. raising the question as to where the additional AA's substrates required for supporting this MPS response are coming from. It would appear that the AA's to support this response are derived from endogenous intracellular/plasma pools and/or protein breakdown (which will increase in fasted periods). ... To conclude, a large single oral dose (~3 g) of Ca-HMB robustly (near maximally) stimulates skeletal muscle anabolism, in the absence of additional nutrient intake; the anabolic effects of Ca-HMB are equivalent to FA-HMB, despite purported differences in bioavailability (Fig. 4).
- ^ Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, Etheridge T, Rathmacher JA, Smith K, Szewczyk NJ, Atherton PJ (June 2013). "Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism" (PDF). The Journal of Physiology. 591 (11): 2911–2923. doi:10.1113/jphysiol.2013.253203. PMC 3690694. PMID 23551944.
The stimulation of MPS through mTORc1-signalling following HMB exposure is in agreement with pre-clinical studies (Eley et al. 2008). ... Furthermore, there was clear divergence in the amplitude of phosphorylation for 4EBP1 (at Thr37/46 and Ser65/Thr70) and p70S6K (Thr389) in response to both Leu and HMB, with the latter showing more pronounced and sustained phosphorylation. ... Nonetheless, as the overall MPS response was similar, this cellular signalling distinction did not translate into statistically distinguishable anabolic effects in our primary outcome measure of MPS. ... Interestingly, although orally supplied HMB produced no increase in plasma insulin, it caused a depression in MPB (−57%). Normally, postprandial decreases in MPB (of ~50%) are attributed to the nitrogen-sparing effects of insulin since clamping insulin at post-absorptive concentrations (5 μU ml−1) while continuously infusing AAs (18 g h−1) did not suppress MPB (Greenhaff et al. 2008), which is why we chose not to measure MPB in the Leu group, due to an anticipated hyperinsulinaemia (Fig. 3C). Thus, HMB reduces MPB in a fashion similar to, but independent of, insulin. These findings are in-line with reports of the anti-catabolic effects of HMB suppressing MPB in pre-clinical models, via attenuating proteasomal-mediated proteolysis in response to LPS (Eley et al. 2008).
GA review
editOngoing GA review
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Reviewer: Tom (LT) (talk · contribs) 05:47, 28 November 2017 (UTC)
Assessmentedit
Discussionedit
@Tom (LT): I finished going through the points below. I just need your feedback on my responses about some of the statements in the medical and pharmacodynamics sections in order to proceed with addressing those issues. Seppi333 (Insert 2¢) 23:12, 21 December 2017 (UTC) Review of texteditHappy to discuss any of the below. These suggestions are not intended to be prescriptive & only intended to illustrate my concerns about the 'well-written' point. They don't all need to be addressed for the review to pass. Hope it is helpful. --Tom (LT) (talk) 22:59, 3 December 2017 (UTC)
Leadedit
UseseditMedicaledit
Side-effectsedit
Pharmacologyedit
Chemistryedit
Historyedit
In generaledit
I hope this review helps. Will start working through your replies in the next day or so. Cheers --Tom (LT) (talk) 22:50, 8 December 2017 (UTC) @Tom (LT): I combed through the references and compiled the list below that includes every primary source cited in the article which has a PMID number (the handful of other primary sources cite statements in chemistry, history, etc., so they're all covered by WP:RS). Primary sources with a PMID # that were cited in this article – the sections in the body where these are cited are listed in parentheses:
Seppi333 (Insert 2¢) 00:02, 9 December 2017 (UTC) COMMENT: Under the rubric of "less is more," I find it unnecessary and annoying that so many of the references include extended quotation of material from the abstracts or articles. Some exceeding 150 words and containing mention of references in the cited article. If the information is essential to the article it belongs in the article. If not, it does not belong anywhere. I've rarely seen reference bloat of this nature, and this is a particularly egregious example. David notMD (talk) 15:45, 12 December 2017 (UTC)
ConclusioneditThanks for your patience, Seppi333. This is a great article that you've put a lot of effort into. With your many changes I feel the article has improved to meet GA criteria. I have one or two concerns that I feel we are at loggerheads here with and will pop on the article's talk page, but nothing that would mean this article shouldn't become a GA. Thanks for your responsiveness; Merry Christmas! --Tom (LT) (talk) 22:26, 25 December 2017 (UTC)
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Small additional concerns
editSome small additional concerns. I don't think these are enough to prevent a successful GA nomination, and they have been discussed with Seppi333 during the nomination and we have reached a loggerheads. I note these with a view to a (1) FA nomination and (2) MEDRS compliance:
- I still think some work could be done paring down references
- I think information relating to the lack of effects of overdose should be included in text
- I am concerned that primary sources are used to make medical claims, which is not something recommended by our WP:MEDRS
- "One clinical trial with Juven for AIDS also demonstrated improvements in immune status, as measured by a reduced HIV viral load relative to controls and higher CD3+ and CD8+ cell counts"
- "The efficacy of Juven for the treatment of cancer cachexia was also examined in a phase 3 clinical trial which found a strong trend (i.e., p=.08) for an improvement in lean body mass relative to controls"
- I do not think that the article needs so many notes (I think most could be removed without damaging the article's integrity)
It would be useful if a third editor could comment on these; Seppi333 makes some good points and it may be useful if a third or fourth editor could offer their opinion on the above. Have a lovely festive season, --Tom (LT) (talk) 22:53, 25 December 2017 (UTC)
- @Tom (LT): Re: "The efficacy of Juven for the treatment of cancer cachexia was also examined in a phase 3 clinical trial which found a strong trend (i.e., p=.08) for an improvement in lean body mass relative to controls"
- Given that this is a primary study showing a non-statistically significant trend, and the cited systematic review essentially says it's useless, this should probably be removed. PriceDL (talk) 00:11, 26 December 2017 (UTC)
- Generally speaking, I am never been in favor of removing references because there are too many and need to be pared down. Sure, some refs may not be MEDRS and removed, but medical topics need to be rich with references and if ten superscripted numerals aren't appropriate in the 'reader's' of the article, retain the references in the wiki-markup view. These references can then be 'reactivated' as other references become outdated. Perhaps I am sensitive to the referencing issues brought up, but there is no need to remove them just because there are too many. Best Regards, Barbara (WVS) ✐ ✉ 15:02, 2 March 2018 (UTC)
Citing a new chemistry claim
editβ-Hydroxy β-methylbutyric acid is a member of the carboxylic acid family of organic compounds and like them, it is a weak acid.
@EdChem: Would you happen to know of a source that can be used to cite this statement? Seppi333 (Insert 2¢) 09:56, 17 April 2018 (UTC)
- Is a citation needed? The diagram of the molecule in the infobox shows a carboxyl group. Care to differ or discuss with me? The Nth User 02:12, 1 June 2018 (UTC)
- The only claim in that sentence that really needs a citation is the assertion that carboxylic acids are weak acids. "β-Hydroxy β-methylbutyric acid is a monocarboxylic β-hydroxy acid" is cited in the previous paragraph. Seppi333 (Insert 2¢) 21:18, 1 June 2018 (UTC)
- The weak acid article supports the general pattern that carboxylic acids are weak, and the enumeration of the strong acid general types and specific examples does not include any. But surprisingly, neither acid strength (target of the weak acid redirect) nor carboxylic acid actually directly cite this specific pattern of this functional group! So "like them" is still not strictly WP:V. DMacks (talk) 05:07, 7 June 2018 (UTC)
- @DMacks: So, do you think this statement should be rephrased to something along the lines of the following sentence?
- "
β-Hydroxy β-methylbutyric acid is a weak acid and a member of the carboxylic acid family of organic compounds.
"
- "
- If it's rephrased in that manner, the only thing that needs to be cited is the assertion that HMB is a weak acid. I might be able to find a citation for that assertion own my own. Seppi333 (Insert 2¢) 01:22, 10 June 2018 (UTC)
- "Weak acid" is a mechanical definition based on the pKa. The pKa value is given and cited in the previous section. So maybe the "weak acid" detail should be moved to there rather than where it is now if we are stating a bare fact rather than making a "chemical structure" explanation? So in the second-level "Chemistry" section:
- and then later in the "Chemical structure" section:
β-hydroxy β-methylbutyric acid is a member of the carboxylic acid family of organic compounds. It is a structural analog...
- DMacks (talk) 02:39, 10 June 2018 (UTC)
- That sounds reasonable. I'll make the change. Seppi333 (Insert 2¢) 19:41, 11 June 2018 (UTC)
- @DMacks: So, do you think this statement should be rephrased to something along the lines of the following sentence?
- The weak acid article supports the general pattern that carboxylic acids are weak, and the enumeration of the strong acid general types and specific examples does not include any. But surprisingly, neither acid strength (target of the weak acid redirect) nor carboxylic acid actually directly cite this specific pattern of this functional group! So "like them" is still not strictly WP:V. DMacks (talk) 05:07, 7 June 2018 (UTC)
- The only claim in that sentence that really needs a citation is the assertion that carboxylic acids are weak acids. "β-Hydroxy β-methylbutyric acid is a monocarboxylic β-hydroxy acid" is cited in the previous paragraph. Seppi333 (Insert 2¢) 21:18, 1 June 2018 (UTC)
@Seppi333: I don't really think any citation was needed as the fact that it is a carboxylic acid and a weak acid is utterly uncontroversial and unlikely to be challenged by anyone. Nevertheless, I also agree with DMacks that the pKa value confirms that it is a weak acid, and the form of words proposed and implemented from your discussion is accurate. Sorry for the delay in responding. EdChem (talk) 12:04, 20 July 2018 (UTC)
- No problem. It probably wouldn't be challenged, but article content in FAs needs to be verifiable. Seppi333 (Insert 2¢) 02:04, 21 July 2018 (UTC)
Conjugate base
editThere appears to be disagreement on whether Beta-Hydroxy beta-methylbutyrate should be described like an alternate name of Beta-Hydroxy beta-methylbutyric acid in the lead. While the two are closely related (They're each other's conjugate acid/base.), I think that the article needs to recognize that they're not exactly the same molecule. Care to differ or discuss with me? The Nth User 02:10, 1 June 2018 (UTC)
- The current version is fine with me. Seppi333 (Insert 2¢) 21:18, 1 June 2018 (UTC)
- I still think that saying that the two conjugates are the same as each other is a simple factual error. Besides prominence of the subject, the case would be exactly the same if Wikipedia said that water was the same as hydronium or hydroxide. Care to differ or discuss with me? The Nth User 02:57, 2 June 2018 (UTC)
- @The Nth User: I completely understand what you're saying. Strictly from a chemistry viewpoint, the two compounds are different in many ways. From a pharmacological/molecular biological, medical, and even biochemical viewpoint though, the two are entirely interchangeable since their pharmacological/cellular properties/effects (e.g., the signaling cascades that they trigger in humans, the resulting effects on muscle protein synthesis/breakdown in humans in vivo, and their presumed biomolecular targets), clinical properties/effects (e.g., effects on lean body mass, recovery time, muscle strength/power, etc. in humans in vivo), and metabolic properties/effects (i.e., biosynthesis and metabolism, due to the fact that these compounds are readily converted to one another in the body, dependent upon the pH of the biofluid compartment where they're distributed) are equivalent; in other words, for the purpose of describing each of those aspects, the acid and base are interchangeable and simultaneous reference to both via the abbreviation "HMB" is desirable/merited.
- I've done my best to balance the fact that they're not equivalent from a chemical viewpoint but are from most other viewpoints by including coverage of both chemical structure diagrams in the drugbox (i.e., the two are very prominently displayed in the drugbox, which makes it abundantly clear that there's a structural difference between them in one of the acid's two hydroxyl groups and a difference in their molecular formulas). I also stopped using the catch-all abbreviation "HMB" in the Beta-Hydroxy beta-methylbutyric acid#Chemistry section and instead used the expanded names of the conjugate acid and base to differentially cover their chemical properties. That's literally the only section of the article where doing this was actually necessary because the vast majority of assertions elsewhere in the article apply simultaneously to both the acid and the base. If you have a better idea about how to go about doing this, let me know. I'm open to modifying the coverage of the distinction in the lead provided that it doesn't create ambiguity about the equivalence of the pharmacological, medical, and biochemical properties. Seppi333 (Insert 2¢) 01:44, 10 June 2018 (UTC)
- Actually, what I said above wasn't completely accurate; differential coverage of HMB-Ca and HMB-FA was necessary in a few sections of the article since the calcium moiety in HMB-Ca modifies the pharmacokinetic properties (i.e., uptake/distribution) and slightly modifies the magnitude of the clinical and cellular/pharmacodynamic effects of the compound relative to HMB-FA (i.e., pure β-hydroxy β-methylbutyric acid). Even so, there are many statements in the article that cover aspects of those topics where differential coverage of HMB-Ca and HMB-FA was/is not necessary. Seppi333 (Insert 2¢) 01:48, 10 June 2018 (UTC)
- @Seppi333: The article now is fine. I just wanted a clarification that they were two separate chemicals at the top. But if anything good came out of this, I got the idea for conjugate acid and base parameters to be added to Template:Chembox. Care to differ or discuss with me? The Nth User 18:43, 16 June 2018 (UTC)
- I still think that saying that the two conjugates are the same as each other is a simple factual error. Besides prominence of the subject, the case would be exactly the same if Wikipedia said that water was the same as hydronium or hydroxide. Care to differ or discuss with me? The Nth User 02:57, 2 June 2018 (UTC)
Long and repetitive introduction
editMost of the content in the introduction is repeated literally word-for-word in the article body. In my revisions I removed all the duplicate info], repeated word for word in the body. I read other bioactive chemical pages and they don’t have the extreme repetitiveness of this article. The intro almost reads as an advertisement for HMB, let your customers read the article first. Anyway, I saw no reason given for undoing my copyedits, why were they removed? Dogshu (talk) 13:04, 29 August 2018 (UTC)
- @Dogshu: sorry for the delayed reply. The lead/intro section of an article is supposed to summarize the body of the article. Article leads should not contain any information which is not stated in the body, with exception for very basic facts about the article topic (e.g., synonyms, topical scope, etc.). Consequently, a well-written article lead should be fairly redundant with the body and adhere to WP:SUMMARYSTYLE. Seppi333 (Insert 2¢) 23:05, 30 August 2018 (UTC)
- @Seppi333:Yes it should be redundant. However entire sections of the intro are repeated verbatim in the body. My revision preserved the references to the content without repeating whole sections verbatim. I know I’m a newb though, and accept your decision, unless anyone else dissents. I am curious however if those that want all the information up front in the intro, making it sound like a miracle drug, have ties to the food supplement industry and are thus biased. Dogshu (talk) 02:18, 31 August 2018 (UTC)
- @Dogshu: Hmm. Well, the sentences in the lead don't necessarily have to differ from the body, but I suppose "good writing" entails at least a little variation when assertions are restated. This reminds me of a general question that I asked about redundant article content when I was a new editor (User talk:Seppi333/Archive 1#Content Redundancy Q), although IIRC the issue that led to me asking that had more to do with restated assertions within different sections of the article's body. Anyway, when I wrote this article, I basically just either summarized several paragraphs of text from the body in 1-2 sentences or copy/pasted the key points and contextual facts from every section of the body. That said, if you want to superficially rephrase the duplicate sentences in the lead section so that they're not verbatim duplicates of the text in the article's body, that would be completely fine with me.
- As for the efficacy of this drug, this article's lead currently states a direction of an effect without quantifying how large the effects are (AKA the magnitude or effect size); more clinical research needs to be conducted in resistance-trained individuals (i.e., people who perform strength/resistance training on a regular basis), endurance athletes, and untrained athletes before a meta-analysis can be performed to determine the effect size of HMB supplementation for each population group. Based upon current evidence, the effect of HMB on muscle mass tends to be smaller in individuals who perform strength training on a regular basis relative to untrained groups. That said, the effect size in older adults has been estimated by a meta-analysis of clinical trials and is included in a note within the body of this article (see beta-Hydroxy beta-methylbutyric acid#cite note-36), but this content isn't covered in the article's lead section; based upon the estimated standard mean difference and the weighted average duration listed in that note, daily HMB supplementation in older adults appears to produce an annual increase in skeletal muscle mass by ~1.5 pounds on average. That's a rather notable fact since sedentary older adults lose muscle mass on an annual basis, and some lose much more. Seppi333 (Insert 2¢) 00:44, 2 September 2018 (UTC)
- Addendum: I included the note I mentioned above at the end of the corresponding sentence in the lead in this edit. Seppi333 (Insert 2¢) 00:48, 2 September 2018 (UTC)
- @Seppi333:Yes it should be redundant. However entire sections of the intro are repeated verbatim in the body. My revision preserved the references to the content without repeating whole sections verbatim. I know I’m a newb though, and accept your decision, unless anyone else dissents. I am curious however if those that want all the information up front in the intro, making it sound like a miracle drug, have ties to the food supplement industry and are thus biased. Dogshu (talk) 02:18, 31 August 2018 (UTC)
Updates - recent (post-FA) reviews and meta-analyses
editFrom this search:
Meta-analyses from 2018
- PMID 29249685; meta-analysis: performance-enhancement literature High Priority Added
- PMID 29676656; meta-analysis + systematic review: healthy adults - presumably mostly athletes (effect on exercise-induced muscle damage) High Priority Added
Systematic reviews from 2018
- PMID 29300431 - systematic review: elderly/clinical High Priority
- PMID 29941852 - systematic review: clinical population - post-surgical recovery High Priority
Other reviews from 2017–2018
Add these when time permits:
Lead breaks on mobile phones in desktop view
editThis is what the beginning of the article looks like in desktop view on my Huawei P20 Pro: https://i.imgur.com/zyevlQK.jpg
Is it necessary to put the conjugate base in a {{nowrap}}? The full, acid name is not in a nowrap. Cheers, Manifestation (talk) 10:49, 26 February 2019 (UTC)
- That's a good point. I support nowrap or other methods to keep each beta with its next word, but no need to keep separate words together. I changed it to allow breaking at the whitespace, as the acid itself is, as you note. DMacks (talk) 15:34, 26 February 2019 (UTC)
- @DMacks: Great! It works. Thanks a lot, Manifestation (talk) 16:25, 27 February 2019 (UTC)
Myoplex
editThis article mentions the supplement Myoplex three times: once in the lead, once under "Use", and once under "History". However, the brand under which the formulation was distributed, EAS, has been discontinued as of June 2018 by its parent, Abbott Laboratories (see here and here). Therefore, I assume Myoplex is no longer being produced. Many shops still have it in stock, but I guess they will run out eventually. Cheers, Manifestation (talk) 17:09, 27 February 2019 (UTC)
- Removed it Seppi333 (Insert 2¢) 20:27, 1 August 2023 (UTC)
Sources of HMB
editThere is little to no information about where companies are sourcing HMB for human consumption. Where is the compound coming from? Animals? Plants? Mining? 2603:6011:5840:77:E883:6958:855B:D2FC (talk) 14:51, 29 May 2023 (UTC)
- There’s an entire section on chemical synthesis … Seppi333 (Insert 2¢) 20:27, 1 August 2023 (UTC)
Source update
editThere are scores of very recent secondary reviews in PubMed, and yet most of the sourcing in the Uses section of this article are dated. SandyGeorgia (Talk) 13:39, 1 August 2023 (UTC)
- Where is supplements purged, under what brand name. 67.4.0.15 (talk) 19:30, 1 August 2023 (UTC)
- Might update it in a year or two. Seems fine right now. Seppi333 (Insert 2¢) 20:14, 1 August 2023 (UTC)